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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:CDC5L-VEGFA

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CDC5L-VEGFA
FusionPDB ID: 14927
FusionGDB2.0 ID: 14927
HgeneTgene
Gene symbol

CDC5L

VEGFA

Gene ID

988

7422

Gene namecell division cycle 5 likevascular endothelial growth factor A
SynonymsCDC5|CDC5-LIKE|CEF1|PCDC5RP|dJ319D22.1MVCD1|VEGF|VPF
Cytomap

6p21.1

6p21.1

Type of geneprotein-codingprotein-coding
Descriptioncell division cycle 5-like proteinCDC5 cell division cycle 5-likeCdc5-related proteindJ319D22.1 (CDC5-like protein)pombe cdc5-related proteinvascular endothelial growth factor Avascular endothelial growth factor A121vascular endothelial growth factor A165vascular permeability factor
Modification date2020031320200329
UniProtAcc

Q99459

Main function of 5'-partner protein: FUNCTION: DNA-binding protein involved in cell cycle control. May act as a transcription activator. Plays role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes (PubMed:11991638, PubMed:20176811, PubMed:28502770, PubMed:28076346, PubMed:29361316, PubMed:29360106, PubMed:29301961, PubMed:30728453, PubMed:30705154). Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. The PRP19-CDC5L complex may also play a role in the response to DNA damage (DDR) (PubMed:20176811). {ECO:0000269|PubMed:10570151, ECO:0000269|PubMed:11082045, ECO:0000269|PubMed:11101529, ECO:0000269|PubMed:11544257, ECO:0000269|PubMed:11991638, ECO:0000269|PubMed:12927788, ECO:0000269|PubMed:18583928, ECO:0000269|PubMed:20176811, ECO:0000269|PubMed:24332808, ECO:0000269|PubMed:28076346, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961, ECO:0000269|PubMed:29360106, ECO:0000269|PubMed:29361316, ECO:0000269|PubMed:30705154, ECO:0000269|PubMed:30728453, ECO:0000269|PubMed:9038199, ECO:0000269|PubMed:9468527, ECO:0000269|PubMed:9632794}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000371477, ENST00000230480, 
ENST00000372064, ENST00000372077, 
ENST00000425836, ENST00000457104, 
ENST00000482630, ENST00000518689, 
ENST00000518824, ENST00000520948, 
ENST00000523125, ENST00000523873, 
ENST00000523950, ENST00000372055, 
ENST00000372067, ENST00000417285, 
ENST00000324450, ENST00000413642, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 4 X 7=28010 X 9 X 5=450
# samples 1113
** MAII scorelog2(11/280*10)=-1.34792330342031
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/450*10)=-1.79141337818858
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CDC5L [Title/Abstract] AND VEGFA [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CDC5L [Title/Abstract] AND VEGFA [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CDC5L(44376369)-VEGFA(43752278), # samples:1
Anticipated loss of major functional domain due to fusion event.CDC5L-VEGFA seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
CDC5L-VEGFA seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
CDC5L-VEGFA seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
CDC5L-VEGFA seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
CDC5L-VEGFA seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
CDC5L-VEGFA seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
CDC5L-VEGFA seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor due to the frame-shifted ORF.
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneCDC5L

GO:0000398

mRNA splicing, via spliceosome

28076346

HgeneCDC5L

GO:0045944

positive regulation of transcription by RNA polymerase II

11082045

TgeneVEGFA

GO:0000122

negative regulation of transcription by RNA polymerase II

18093989

TgeneVEGFA

GO:0001525

angiogenesis

11427521|21771332

TgeneVEGFA

GO:0001666

response to hypoxia

16490744

TgeneVEGFA

GO:0001934

positive regulation of protein phosphorylation

18386220|19033661

TgeneVEGFA

GO:0001938

positive regulation of endothelial cell proliferation

9202027|10022831|12714610|16489009|18386220|18577655|20497126

TgeneVEGFA

GO:0002042

cell migration involved in sprouting angiogenesis

18059339|20660291

TgeneVEGFA

GO:0002092

positive regulation of receptor internalization

20660291

TgeneVEGFA

GO:0008284

positive regulation of cell proliferation

7929439

TgeneVEGFA

GO:0008360

regulation of cell shape

7929439|10527820

TgeneVEGFA

GO:0010595

positive regulation of endothelial cell migration

10022831|19033661

TgeneVEGFA

GO:0010628

positive regulation of gene expression

18386220

TgeneVEGFA

GO:0010629

negative regulation of gene expression

28977001

TgeneVEGFA

GO:0010749

regulation of nitric oxide mediated signal transduction

16150726

TgeneVEGFA

GO:0030224

monocyte differentiation

21149635

TgeneVEGFA

GO:0030225

macrophage differentiation

21149635

TgeneVEGFA

GO:0030335

positive regulation of cell migration

7929439|17470632

TgeneVEGFA

GO:0030949

positive regulation of vascular endothelial growth factor receptor signaling pathway

1312256|7929439

TgeneVEGFA

GO:0031334

positive regulation of protein complex assembly

16489009|19033661

TgeneVEGFA

GO:0031954

positive regulation of protein autophosphorylation

20497126

TgeneVEGFA

GO:0032147

activation of protein kinase activity

18059339|20497126

TgeneVEGFA

GO:0032793

positive regulation of CREB transcription factor activity

20497126

TgeneVEGFA

GO:0033138

positive regulation of peptidyl-serine phosphorylation

18440775|20497126

TgeneVEGFA

GO:0035148

tube formation

19033661

TgeneVEGFA

GO:0035767

endothelial cell chemotaxis

18440775

TgeneVEGFA

GO:0035924

cellular response to vascular endothelial growth factor stimulus

18440775|20497126

TgeneVEGFA

GO:0038033

positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway

18440775|20497126|21245381

TgeneVEGFA

GO:0038091

positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway

17470632

TgeneVEGFA

GO:0042531

positive regulation of tyrosine phosphorylation of STAT protein

19390056

TgeneVEGFA

GO:0043117

positive regulation of vascular permeability

26598555

TgeneVEGFA

GO:0043154

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

18386220

TgeneVEGFA

GO:0043406

positive regulation of MAP kinase activity

18440775

TgeneVEGFA

GO:0043536

positive regulation of blood vessel endothelial cell migration

9202027|18440775|20497126

TgeneVEGFA

GO:0045766

positive regulation of angiogenesis

18440775|18577655|19033661|20497126

TgeneVEGFA

GO:0045785

positive regulation of cell adhesion

19674970

TgeneVEGFA

GO:0045944

positive regulation of transcription by RNA polymerase II

18059339

TgeneVEGFA

GO:0048010

vascular endothelial growth factor receptor signaling pathway

21245381

TgeneVEGFA

GO:0050731

positive regulation of peptidyl-tyrosine phosphorylation

10022831|16489009|20048167|21245381|26598555

TgeneVEGFA

GO:0050918

positive chemotaxis

20497126

TgeneVEGFA

GO:0050927

positive regulation of positive chemotaxis

7929439|12744932

TgeneVEGFA

GO:0051272

positive regulation of cellular component movement

10527820|12744932

TgeneVEGFA

GO:0051894

positive regulation of focal adhesion assembly

16489009

TgeneVEGFA

GO:0071456

cellular response to hypoxia

10575000

TgeneVEGFA

GO:0090037

positive regulation of protein kinase C signaling

18059339

TgeneVEGFA

GO:0090050

positive regulation of cell migration involved in sprouting angiogenesis

20551324

TgeneVEGFA

GO:0097533

cellular stress response to acid chemical

26299712

TgeneVEGFA

GO:1900086

positive regulation of peptidyl-tyrosine autophosphorylation

20660291

TgeneVEGFA

GO:1900745

positive regulation of p38MAPK cascade

18386220

TgeneVEGFA

GO:1901727

positive regulation of histone deacetylase activity

20497126

TgeneVEGFA

GO:1903141

negative regulation of establishment of endothelial barrier

20048167

TgeneVEGFA

GO:1903392

negative regulation of adherens junction organization

26598555

TgeneVEGFA

GO:1903572

positive regulation of protein kinase D signaling

20497126

TgeneVEGFA

GO:1903672

positive regulation of sprouting angiogenesis

26299712

TgeneVEGFA

GO:2000048

negative regulation of cell-cell adhesion mediated by cadherin

26598555



check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr6:44376369/chr6:43752278)
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
- How to search
1. Put your fusion gene symbol.
2. Press the tab key until there will be shown the breakpoint information filled.
4. Go down and press 'Search' tab twice.
4. Go down to have the hyperlink of the search result.
5. Click the hyperlink.
6. See the FGviewer result for your fusion gene.
FGviewer

check buttonRetention analysis results of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features, are available here.

check buttonFusion gene breakpoints across CDC5L (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across VEGFA (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000371477CDC5Lchr644376369+ENST00000324450VEGFAchr643752278+141313912751396373
ENST00000371477CDC5Lchr644376369+ENST00000413642VEGFAchr643752278+144013912751396373

check buttonDeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score
ENST00000371477ENST00000324450CDC5Lchr644376369+VEGFAchr643752278+0.0015724380.9984276
ENST00000371477ENST00000413642CDC5Lchr644376369+VEGFAchr643752278+0.0015944280.99840564

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for CDC5L-VEGFA

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide

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Potential FusionNeoAntigen Information of CDC5L-VEGFA in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Potential FusionNeoAntigen Information of CDC5L-VEGFA in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)

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Fusion breakpoint peptide structures of CDC5L-VEGFA

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CDC5L-VEGFA

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score

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Vaccine Design for the FusionNeoAntigens of CDC5L-VEGFA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence

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Information of the samples that have these potential fusion neoantigens of CDC5L-VEGFA

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample

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Potential target of CAR-T therapy development for CDC5L-VEGFA

check button Predicted 3D structure. We used RoseTTAFold.

check buttonRetention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to CDC5L-VEGFA

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to CDC5L-VEGFA

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource